Tensin-3 Regulates Integrin-Mediated Proliferation and Differentiation of Tonsil-Derived Mesenchymal Stem Cells

Abstract

Human palatine tonsils are potential tissue source of multipotent mesenchymal stem cells (MSCs). The proliferation rate of palatine tonsil-derived MSCs (TMSCs) is far higher than that of bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs (ADSCs). In our previous study, we had found through DNA microarray analysis that tensin-3 (TNS3), a type of focal adhesion protein, was more highly expressed in TMSCs than in both BMSCs and ADSCs. Here, the role of TNS3 in TMSCs and its relationship with integrin were investigated. TNS3 expression was significantly elevated in TMSCs than in other cell types. Cell growth curves revealed a significant decrease in the proliferation and migration of TMSCs treated with siRNA for TNS3 (siTNS3). siTNS3 treatment upregulated p16 and p21 levels and downregulated SOX2 expression and focal adhesion kinase, protein kinase B, and c-Jun N-terminal kinase phosphorylation. siTNS3 transfection significantly reduced adipogenic differentiation of TMSCs and slightly decreased osteogenic and chondrogenic differentiation. Furthermore, TNS3 inhibition reduced active integrin beta-1 (ITGβ1) expression, while total ITGβ1 expression was not affected. Inhibition of ITGβ1 expression in TMSCs by siRNA showed similar results observed in TNS3 inhibition. Thus, TNS3 may play an important role in TMSC proliferation and differentiation by regulating active ITGβ1 expression.

MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity

“…Though MLL3 or TNS3 knockdown did not elevate downstream gene dramatically, quite a few migration-related genes were upregulated. A mechanism published previously involving JNK/cJun pathway is probably also functioning here 37 .…”

“…1D ). TNS3 was reported as a gene involved in migration and has been associated with several types of cancers 37 – 39 . As expected, TNS3 knockdown increased cell migration (Fig.…”

“…MLL3 regulates H3K4me1 and H3K27ac on TNS3 enhancer, which in turn affects TNS3 transcription. TNS3 has been shown as an important protein involved in integrin-mediated signaling and cell migration 37 . The gene expression and DNA methylation on CpG island of TNS3 have been associated with breast cancer and renal cell carcinoma 38 , 39 .…”

Tensins – emerging insights into their domain functions, biological roles and disease relevance

“…Taken together, TNS2 negatively regulates cell proliferation likely by suppressing IRS-1, Akt and MEK-ERK signaling pathways. TNS3 knockdown in tonsil-derived mesenchymal stem cells (TMSCs) results in an increase in the cyclin-dependent kinase (CDK) inhibitors p16 and p21 (CDKN2A and CDKN1A), and reduces cell proliferation (Park et al, 2019). Silencing of CTEN also enhances the accumulation of the CDK inhibitors p21 and p27 (CDKN1B) and attenuates RWPE-1 non-malignant prostate epithelial cell proliferation (Wu and Liao, 2018).…”

Tonsil mesenchymal stem cells-derived extracellular vesicles prevent submandibular gland dysfunction in ovariectomized rats

“…MSCs are a good candidate for cell therapy in tissue engineering and regenerative medicine, and the therapeutic function of MSCs can be attributed mainly to their paracrine effect [ 12 ]. Extracellular vesicles containing exosomes derived from MSCs have paracrine effects [ 13 ].…”